Functional studies on DJ-1, a redox-regulated molecular chaperone implicated in Parkinson's disease.

摘要

This thesis investigates the function of the Parkinson's Disease-associated protein DJ-1, and its role in Familial Parkinsonism. In vitro and in vivo characterization of DJ-1 indicates that DJ-1 functions as a redox-regulated molecular chaperone within the cell to inhibit accumulation of misfolded proteins. Generation and characterization of DJ-1-deficient Embryonic Stem cells and ES-cell derived dopamine neurons demonstrates the specific consequences of loss of DJ-1 function in dopamine neurons. Finally, mechanistic studies on DJ-1 function highlight the importance of dimerization and disulfide bond formation at the dimerization interface.